Background: Cetuximab (CTX) is a glycosylated anti-EGFR monoclonal antibody of great interest in the treatment of non-melanoma skin cancers. Its intravenous administration is associated with severe side effects. This is the first report on the noninvasive iontophoretic-targeted topical delivery of CTX to skin. Methods: Iontophoretic transport of CTX (0.5 mA/cm2) was studied as a function of formulation pH (4, 5.5 and 7) and duration of current application (2, 4 and 8 h). CTX cutaneous biodistribution was determined; electrotransport mechanisms and penetration pathways were investigated. Results: Electrophoretic mobility measurements of CTX isoforms and co-iontophoresis of acetaminophen at each pH demonstrated that CTX electrotransport was due to electroosmosis: despite an ~8-fold reduction in charge, CTX skin deposition was greater at pH 7 than pH 4 (8.974 ± 1.952 and 0.482 ± 0.165 μg/mm3) – consistent with the increased electroosmotic flow at pH 7. Iontophoresis of an Alex488-CTX conjugate showed that skin penetration occurred by the intercellular and follicular routes. Therapeutic concentrations of CTX in the viable epidermis, upper dermis and lower dermis were achieved following iontophoresis for 2, 4 and 8 h, respectively. Conclusion: The results demonstrate the topical delivery of a 152 kDa monoclonal antibody into skin in a targeted, controlled and entirely noninvasive manner.